Coenzyme Q10–for health professionals (PDQ®)

Overview

This complementary
and alternative medicine (CAM) information summary provides an overview of
the use of coenzyme Q10 in cancer therapy. The summary includes a
history of coenzyme Q10 research, a review of laboratory studies,
and data from investigations involving human subjects. Although several
naturally occurring forms of coenzyme Q have been identified, Q10
is the predominant form found in humans and most mammals, and it is the form
most studied for therapeutic potential. Thus, it will be the only form of coenzyme Q discussed in this
summary.

Many of the medical and scientific terms used in the summary are hypertext linked (at first use in each section) to the NCI Dictionary of Cancer Terms, which is oriented toward nonexperts. When a linked term is clicked, a definition will appear in a separate window.

Reference citations in some PDQ CAM information summaries may include links to external Web sites that are operated by individuals or organizations for the purpose of marketing or advocating the use of specific treatments or products. These reference citations are included for informational purposes only. Their inclusion should not be viewed as an endorsement of the content of the Web sites, or of any treatment or product, by the PDQ Cancer CAM Editorial Board or the National Cancer Institute.

General Information

Coenzyme Q10 (also known as CoQ10, Q10,
vitamin Q10, ubiquinone, and ubidecarenone) is a benzoquinone
compound synthesized naturally by the human body. The “Q” and the “10” in the
name refer to the quinone chemical group and the 10 isoprenyl subunits that are part of this compound’s structure. The term
“coenzyme” denotes it as an organic (contains carbon atoms), nonprotein molecule necessary for the proper
functioning of its protein partner (an enzyme or an enzyme complex). Coenzyme
Q10 is used by cells of the body in a process known variously as aerobic respiration, aerobic metabolism, oxidative metabolism, or cell respiration. Through this
process, mitochondria produce energy for cell growth and maintenance.[1-4]
Coenzyme Q10 is also used by the body as an endogenousantioxidant.[1,2,4-8] An antioxidant is a substance that protects cells from free radicals, which are highly
reactive chemicals, often containing oxygen atoms, capable of damaging
important cellular components such as DNA and lipids. In addition, the plasma level of coenzyme Q10 has
been used in studies as a measure of oxidative stress.[9,10]

Coenzyme Q10 is present in most tissues, but the highest
concentrations are found in the heart, the liver, the kidneys, and the pancreas.[11] The lowest concentration is
found in the lungs.[11] Tissue levels of this compound decrease as people age,
due to increased requirements, decreased production,[11] or insufficient intake
of the chemical precursors needed for synthesis.[12] In humans,
normal blood levels of coenzyme Q10 have been defined variably,
with reported normal values ranging from 0.30 to 3.84 µg /mL.[2,4,13,14]

Given the importance of coenzyme Q10 in optimizing cellular energy
production, use of this compound as a treatment for diseases other than cancer has been explored. Most of these investigations have focused on coenzyme
Q10 as a treatment for cardiovascular disease.[2,4,15] In patients with cancer, coenzyme Q10 has been shown to
protect the heart from anthracycline -induced cardiotoxicity (anthracyclines are
a family of chemotherapy drugs, including doxorubicin, that have the potential to
damage the heart)[3,16-18] and to stimulate the immune system.[19,20] Stimulation of the immune system by this compound has also been observed
in animal studies and in humans without cancer.[21-27] In part because of its immunostimulatory potential, coenzyme Q10 has been used as an adjuvant therapy in patients with
various types of cancer.[17,20,28-33]

While coenzyme Q10 may show indirect anticancer activity through
its effect(s) on the immune system, there is evidence to suggest that analogs of this compound can suppress
cancer growth directly. Analogs of coenzyme Q10 have been shown to
inhibit the proliferation of cancer cells in vitro and the growth of cancer cells transplanted into rats and mice.[12,34] In view of these findings, it has
been proposed that analogs of coenzyme Q10 may function as antimetabolites to disrupt normal biochemical reactions that are required for cell growth and/or survival and,
thus, that they may be useful as chemotherapeutic
agents.[12,34]

Several companies distribute coenzyme Q10 as a dietary
supplement. In the United States, dietary supplements are regulated as foods,
not drugs. Therefore, premarket evaluation and approval by the U.S. Food and Drug
Administration (FDA) are not required unless specific disease prevention or
treatment claims are made. The FDA can, however, remove from the market dietary supplements that it deems unsafe. Because dietary supplements are not formally
reviewed for manufacturing consistency, there may be considerable variation
from lot to lot. The FDA has not approved coenzyme Q10 for the treatment of cancer or any other medical condition.

To conduct clinical drug research in the United States, researchers must
file an Investigational New Drug (IND) application with the FDA. The IND
application process is highly confidential, and IND information can be
disclosed only by the applicants. To date, no investigators have announced
that they have applied for an IND to study coenzyme Q10 as a
treatment for cancer.

In animal studies, coenzyme Q10 has been administered by injection (intravenous, intraperitoneal, intramuscular, or subcutaneous). In humans, it is
usually taken orally as a pill (gel bead or capsule), but
intravenous infusions have been
given.[4] Coenzyme Q10 is absorbed best with fat; therefore, lipid
preparations are better absorbed than the purified compound.[2,4]
In human studies, supplementation doses and administration schedules have
varied, but usually have been in the range of 90 to 390 mg/day.

Folkers K: Relevance of the biosynthesis of coenzyme Q10 and of the four bases of DNA as a rationale for the molecular causes of cancer and a therapy. Biochem Biophys Res Commun 224 (2): 358-61, 1996. [PUBMED Abstract]

A large amount of laboratory and animal data on coenzyme Q10 have
accumulated since 1962.[2] Research into cellular energy-producing mechanisms that involve this compound was awarded the Nobel Prize in
Chemistry in 1978. Some of the accumulated data show that coenzyme
Q10 stimulates animal immune systems, leading to higher antibody levels,[13] greater numbers
and/or activities of macrophages and T cells (T lymphocytes),[13,14] and increased
resistance to infection.[15-17] Coenzyme Q10 has also been
reported to increase IgG (immunoglobulin G) antibody levels
and to increase the CD4 to CD8 T-cell ratio in humans.[18-20] CD4 and CD8
are proteins found on the surface of T cells, with CD4 and CD8 identifying helper T cells and cytotoxic T cells,
respectively; decreased CD4 to CD8 T-cell ratios have been reported for cancer
patients.[21,22] Research subsequently delineated the antioxidant properties
of coenzyme Q10.[23-27]

Proposed mechanisms of action for coenzyme Q10 that are relevant
to cancer include its essential function in cellular energy production and its
stimulation of the immune system (which may both be related), as well as
its role as an antioxidant. Coenzyme Q10 is essential to aerobic energy production,[1,25,28] and it has been suggested that increased cellular energy leads to
increased antibody synthesis in B cells (B lymphocytes).[6,18] As noted previously (General Information section),
coenzyme Q10 can also behave as an antioxidant.[1,25-27,29-32] In this capacity, coenzyme Q10 is thought to stabilize cell
membranes (lipid -containing structures essential to maintaining cell
integrity) and to prevent free radical damage to other important cellular
components.[1,25,27,32] Free radical damage to DNA (and possibly to
other cellular molecules) may be a factor in cancer development.[11,23,30,33-36]

Folkers K: Relevance of the biosynthesis of coenzyme Q10 and of the four bases of DNA as a rationale for the molecular causes of cancer and a therapy. Biochem Biophys Res Commun 224 (2): 358-61, 1996. [PUBMED Abstract]

Laboratory/Animal/Preclinical Studies

Laboratory work on coenzyme Q10 has focused primarily on its
structure and its function in cell respiration. Studies in animals have
demonstrated that coenzyme Q10 is capable of stimulating the immune
system, with treated animals showing increased resistance to protozoalinfections [1,2] and to viral and chemically-induced neoplasia.[1-4] Early
studies of coenzyme Q10 showed increased hematopoiesis (the formation of new blood cells) in monkeys,[4,5] rabbits,[6] and
poultry.[5] Coenzyme Q10 demonstrated a protective
effect on the heart muscle of mice, rats, and rabbits given the anthracycline anticancer drug doxorubicin.[7-12] Although another study confirmed this
protective effect with intraperitoneal administration of doxorubicin in mice,
it failed to demonstrate a protective effect when the anthracycline was given intravenously, which is the route of administration in humans.[13]
Researchers in one study sounded a cautionary note when they found that
coadministration of coenzyme Q10 and radiation therapy decreased the
effectiveness of the radiation therapy.[14] In this study, mice inoculated with
human small cell lung cancer cells
(a xenograft study), and then given
coenzyme Q10 and single-dose radiation therapy, showed
substantially less inhibition of tumor growth than mice in the control group that were treated with radiation therapy alone. Since radiation leads to the
production of free radicals, and since antioxidants protect against free
radical damage, the effect in this study might be explained by coenzyme
Q10 acting as an antioxidant. As noted previously (General Information), there is some evidence from
laboratory and animal studies that analogs of coenzyme Q10 may
have direct anticancer activity.[15,16]

In view of the promising results from animal studies, coenzyme
Q10 was tested as a protective agent against the cardiac toxicity observed in cancer
patients treated with the anthracycline drug doxorubicin. It has been
postulated that doxorubicin interferes with energy-generating biochemical
reactions that involve coenzyme Q10 in heart muscle mitochondria and that this interference can be overcome by coenzyme Q10supplementation.[2,13,14] Studies with adults and children, including the
aforementioned randomized trial, have confirmed the decrease in cardiac
toxicity observed in animal studies.[1-3,7] A randomized trial [7] of 20 patients tested the ability of coenzyme Q10 to reduce cardiotoxicity caused by anthracycline drugs.

The potential of coenzyme Q10 as an adjuvant therapy for cancer
has also been explored. In view of observations that blood levels of coenzyme
Q10 are frequently reduced in cancer patients,[6,10,11,15,16] supplementation with this compound has been tested in patients
undergoing conventional treatment. An open-label (nonblinded), uncontrolled clinical study
in Denmark followed 32 breast cancer patients for 18 months.[4] The disease
in these patients had spread to the axillary lymph nodes, and an
unreported number had distant metastases. The patients received antioxidant supplementation (vitamin C, vitamin E, and beta carotene), other vitamins and trace minerals, essential fatty acids, and coenzyme
Q10 (at a dose of 90 mg/day), in addition to standard
therapy (surgery, radiation therapy, and chemotherapy, with or without tamoxifen). The patients were seen every
3 months to monitor disease status (progressive disease or recurrence), and, if there was a
suspicion of recurrence, mammography, bone scan, x-ray, or biopsy was performed. The survival rate for
the study period was 100% (4 deaths were expected). Six
patients were reported to show some evidence of remission; however, incomplete clinical
data were provided, and information suggestive of remission was presented for
only 3 of the 6 patients. None of the 6 patients had evidence of
further metastases. For all 32 patients, decreased use of painkillers,
improved quality of life, and an
absence of weight loss were reported. Whether painkiller use and quality of
life were measured objectively (e.g., from pharmacy records and validated
questionnaires, respectively) or subjectively (from patient self-reports) was
not specified.

In a follow-up study, 1 of the 6 patients with a reported remission and
a new patient were treated for several months with higher doses of coenzyme
Q10 (390 and 300 mg/day, respectively).[5] Surgical
removal of the primary breast tumor in both patients had been incomplete.
After 3 to 4 months of high-level coenzyme Q10 supplementation,
both patients appeared to experience complete regression of their residual breast
tumors (assessed by clinical examination and mammography). It should be noted
that a different patient identifier was used in the follow-up study for the
patient who had participated in the original study. Therefore, it is
impossible to determine which of the 6 patients with a reported remission
took part in the follow-up study. In the follow-up study report, the
researchers noted that all 32 patients from the original study remained alive
at 24 months of observation, whereas 6 deaths had been expected.[5]

In another report by the same investigators, 3 breast cancer patients
were followed for a total of 3 to 5 years on high-dose coenzyme Q10
(390 mg/day).[6] One patient had complete remission of liver metastases (determined by clinical examination and ultrasonography), another had
remission of a tumor that had spread to the chest wall (determined by clinical
examination and chest x-ray), and the third patient had no microscopic evidence of remaining tumor after a mastectomy (determined by biopsy of the
tumor bed).

All 3 of the above-mentioned human studies [4-6] had important design
flaws that could have influenced their outcome. Study weaknesses include the
absence of a control group (i.e., all patients received coenzyme
Q10), possible selection
bias in the follow-up investigations, and multiple confounding variables
(i.e., the patients received a variety of supplements in addition to coenzyme
Q10, and they received standard therapy either during or
immediately before supplementation with coenzyme Q10). Thus, it is
impossible to determine whether any of the beneficial results was directly
related to coenzyme Q10 therapy.

Anecdotal reports of coenzyme Q10 lengthening the survival of
patients with pancreatic, lung, rectal, laryngeal, colon, and prostate cancers
also exist in the peer-reviewed scientific literature.[3] The patients
described in these reports also received therapies other than coenzyme
Q10, including chemotherapy, radiation therapy, and surgery.

Folkers K: Relevance of the biosynthesis of coenzyme Q10 and of the four bases of DNA as a rationale for the molecular causes of cancer and a therapy. Biochem Biophys Res Commun 224 (2): 358-61, 1996. [PUBMED Abstract]

Adverse Effects

No serious toxicity associated with the use of coenzyme Q10 has
been reported.[1-4] Doses of 100 mg /day or
higher have caused mild insomnia in
some individuals. Liverenzyme elevation has been detected in
patients taking doses of 300 mg/day for extended periods of time,
but no liver toxicity has been reported.[1] Researchers in one cardiovascularstudy reported that coenzyme Q10 caused rashes, nausea, and epigastric (upper abdominal) pain that required withdrawal of a small number of patients from
the study.[5] Other reported side effects have included dizziness, photophobia (abnormal visual
sensitivity to light), irritability,[5] headache, heartburn, and fatigue.[6]

Certain lipid -lowering drugs, such as the statins (lovastatin, pravastatin, and simvastatin) and gemfibrozil, as well as oral agents that
lower blood sugar, such as glyburide and tolazamide, cause a decrease in serum levels of coenzyme Q10
and reduce the effects of coenzyme Q10supplementation.[1,7-9] Beta-blockers (drugs that slow the heart rate and lower blood pressure) can inhibit coenzyme Q10-dependent enzyme
reactions. The contractile force of the heart in patients with high blood pressure can be increased by coenzyme Q10
administration.[1] Coenzyme Q10 can reduce the body’s
response to the anticoagulant drug warfarin.[9] Finally,
coenzyme Q10 can decrease insulin requirements in individuals with diabetes.

Describe clinical findings in sufficient detail that a meaningful evaluation can be made.

Separate levels of evidence scores are assigned to qualifying human studies on the basis of statistical strength of the study design and scientific strength of the treatment outcomes (i.e., endpoints) measured. The resulting two scores are then combined to produce an overall score. A table showing the levels of evidence scores for qualifying human studies cited in this summary is presented below. For an explanation of the scores and additional information about levels of evidence analysis of CAM treatments for cancer, refer to Levels of Evidence for Human Studies of Cancer Complementary and Alternative Medicine.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the use of coenzyme Q10 in the treatment of people with cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Cancer Complementary and Alternative Medicine Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

be discussed at a meeting,

be cited with text, or

replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewer for Coenzyme Q10 is:

Jeffrey D. White, MD (National Cancer Institute)

Any comments or questions about the summary content should be submitted to Cancer.gov through the Web site's Contact Form. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Cancer Complementary and Alternative Medicine Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”

Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Contact Us

More information about contacting us or receiving help with the Cancer.gov Web site can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the Web site’s Contact Form.

Updated: May
14, 2014

This text may be reproduced or reused freely. Please credit the National Cancer Institute as the source. Any graphics may be owned by the artist or publisher who created them, and permission may be needed for their reuse.